In vivo depletion of B cells using a combination of high-dose cytosine arabinoside/mitoxantrone and rituximab for autografting in patients with non-Hodgkin's lymphoma

被引:76
作者
Voso, MT
Pantel, G
Weis, M
Schmidt, P
Martin, S
Moos, M
Ho, AD
Haas, R
Hohaus, S
机构
[1] Heidelberg Univ, Dept Internal Med 5, Heidelberg, Germany
[2] German Canc Res Ctr, D-6900 Heidelberg, Germany
关键词
rituximab; follicular lymphoma; real-time PCR;
D O I
10.1046/j.1365-2141.2000.02084.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We performed a pilot study including rituximab (Mabthera; IDEC-C2B8, Hoffmann-La Roche) with a sequential high-dose therapy protocol in 15 patients with follicular and three patients with mantle cell lymphoma and studied the potential of the chemoimmunotherapy to induce depletion of malignant B cells in vivo. Our treatment protocol included induction with three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, followed by peripheral blood stem cell (PBSC) mobilization using high-dose cytosine arabinoside (2 g/m(2) every 12 h, days 1 and 2) and mitoxantrone (10 mg/m(2), days 2 and 3) (HAM), preceeded by rituximab (375 mg/m(2)). The proportion of CD19(+) B cells in blood and bone marrow decreased from 1.2 +/- 0.4% to 0.13 +/- 0.1% (P = 0.01) and from 2.7 +/- 0.8% to 0.8 +/- 0.5% (P = 0.03) respectively. The number of t(14;18)-positive cells in blood and bone marrow progressively decreased with treatment, as assessed by the quantitative real-time PCR assay in four patients. Conversion to PCR-negativity was achieved in the peripheral blood (PB) of seven informative patients. Leucaphereses were performed during the granulocyte colony-stimulating factor (G-CSF)-supported leucocyte recovery phase. In 17 of 18 patients, a median of 15.1 x 10(6) CD34(+) cells/kg body weight (BW) could be harvested by a single procedure for enrichment by an immunomagnetic method. Leucapheresis products contained 51.3 +/- 28.8 x 10(4) CD19(+) B cells/kg BW (mean) and were t(14;18) PCR negative in all seven informative patients. These data compare favourably with results obtained in patients treated with the same regimen without rituximab. The high-dose therapy (n = 12 patients), including total body irradiation (14.4 Gy) and cyclophosphamide (200 mg/kg BW), was also preceeded by rituximab. Recovery of neutrophils to > 0.5 x 10(9)/l and of platelets to > 20 x 10(9)/l required a median of 13.5 and 11.5 d (range 11-24 and 9-24 d) respectively. In conclusion, the addition of the CD20 antibody to chemotherapy ensured tumour depletion in vivo and allowed the collection of PBSCs devoid of tumour cells and with conserved engraftment capability.
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收藏
页码:729 / 735
页数:7
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